Safety of Drugs Used in Hospitalized Infants

Examining the safety of more than 10 medications in hospitalized infants using a large database with information from electronic health records.


Only 25% of approved drugs marketed in the United States have sufficient pediatric data to support product labeling by the FDA for dosing, safety, or efficacy in children. As a result, the majority of drugs administered to children are used off-label. Clinical trials to evaluate the safety of these drugs are lacking across pediatric age groups, due, in part, to concerns about exposing pediatric patients to the risks of prospective drug studies.

Retrospective observational studies carry minimal risk for participants. The use of a large database usually provides samples sizes large enough to make inferences about the population in question. In this PTN study, we will use the Pediatrix Medical Group database—a database prospectively created from electronic health records of infants admitted to more than 300 neonatal intensive care units (NICUs) in the United States. It is one of the largest repositories of data in neonatal medicine; the database includes approximately 22% of NICU patients nationally and over 90,000 NICU admissions annually.

Using retrospective data analysis techniques, we will estimate the incidence of adverse events for hospitalized infants exposed to drugs of interest, including proton pump inhibitors, octreotide, and 8 additional therapeutics. These results will be compared against those from an FDA pediatric pilot study comprising a network of 6 hospitals seeking to better understand both indications for off-label use and incidences of adverse events. The comparison of frequency of adverse events from the Pediatrix database and the FDA pediatric pilot study will facilitate understanding of the most appropriate information system for studying drug use and adverse events in infants.


  • Cefepime and Ceftazidime Safety in Hospitalized Infants The Pediatric Infectious Disease Journal • August 2015. Arnold CJ, Ericson J, Cho N, Tian J, Wilson S, Chu VH, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee. Cefepime and ceftazidime are cephalosporins used for the treatment of serious Gram-negative infections. These cephalosporins are used off-label ...
  • Safety of octreotide in hospitalized infants Early Human Development • July 2015. Testoni D, Hornik CP, Neely ML, Yang Q, McMahon AW, Clark RH, Smith PB; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee. Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not ...
  • Anaerobic antimicrobial therapy after necrotizing enterocolitis in VLBW infants Pediatrics • January 2015. Autmizguine J, Hornik CP, Benjamin DK Jr, Laughon MM, Clark RH, Cotten CM, Cohen-Wolkowiez M, Benjamin DK, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. To evaluate the effect of anaerobic antimicrobial therapy for necrotizing enterocolitis (NEC) on clinical outcomes in very low birth weight (≤1500 g) infants. We ...
  • Safety of milrinone use in neonatal intensive care units Early Human Development • January 2015. Samiee-Zafarghandy S, Raman SR, van den Anker JN, McHutchison K, Hornik CP, Clark RH, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought ...
  • Medication use in the neonatal intensive care unit American Journal of Perinatology • October 2014. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network. The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use ...



Published; clinical study report submitted to FDA

Principal Investigators:
Daniel K. Benjamin, MD, PhD, MPH and P. Brian Smith, MD, MPH, MHS
Duke Health, Durham, NC


  • The Pharmacometrics Core of the PTN Edmund Capparelli, PharmD, chair of the Pharmacometrics Core of the Pediatric Trials Network, explains the role of pharmacometrics in improving medical treatments for infants and children.
  • The Clinical Pharmacology Core of the PTN Greg Kearns, chair of the PTN Clinical Pharmacology Core, explains how clinical pharmacology helps to make medicines safer for children.